Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA.
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Small. 2022 Nov;18(46):e2204941. doi: 10.1002/smll.202204941. Epub 2022 Oct 10.
Nucleic acid nanoparticles, or NANPs, rationally designed to communicate with the human immune system, can offer innovative therapeutic strategies to overcome the limitations of traditional nucleic acid therapies. Each set of NANPs is unique in their architectural parameters and physicochemical properties, which together with the type of delivery vehicles determine the kind and the magnitude of their immune response. Currently, there are no predictive tools that would reliably guide the design of NANPs to the desired immunological outcome, a step crucial for the success of personalized therapies. Through a systematic approach investigating physicochemical and immunological profiles of a comprehensive panel of various NANPs, the research team developes and experimentally validates a computational model based on the transformer architecture able to predict the immune activities of NANPs. It is anticipated that the freely accessible computational tool that is called an "artificial immune cell," or AI-cell, will aid in addressing the current critical public health challenges related to safety criteria of nucleic acid therapies in a timely manner and promote the development of novel biomedical tools.
核酸纳米颗粒(NANPs),经合理设计与人体免疫系统相互作用,可以为克服传统核酸疗法的局限性提供创新的治疗策略。每组 NANPs 在其结构参数和物理化学性质方面都是独特的,这些特性与递送载体的类型一起决定了它们免疫反应的类型和程度。目前,还没有可靠的预测工具可以指导 NANPs 的设计以达到预期的免疫学效果,这是个性化治疗成功的关键步骤。通过系统地研究各种 NANPs 的物理化学和免疫学特性,研究团队开发并通过实验验证了一种基于变压器架构的计算模型,该模型能够预测 NANPs 的免疫活性。预计,这个被称为“人工免疫细胞”(AI-cell)的免费计算工具将有助于及时应对与核酸疗法安全性标准相关的当前重大公共卫生挑战,并促进新型生物医学工具的发展。